title: Clinicopathological significance of claudin-4 in gastric carcinoma.
abstract: BACKGROUND
  Aberrant expression of claudin proteins has been reported in a variety of cancers. Previous studies have demonstrated that overexpression of claudin may promote tumorigenesis and metastasis through increased invasion and survival of tumor cells. However, the prognostic significance of claudin-4 in gastric cancer remains unclear.
  
  
  METHODS
  Immunohistochemistry was used to analyze the expression of claudin-4 in 329 clinical gastric cancer specimens and 44 normal stomach samples, 21 intestinal metaplasia samples, and 21 adjacent precursor lesions dysplasia samples. Statistical analysis methods were used to evaluate the relationship between claudin-4 expression and various clinicopathological parameters. Univariate and multivariate analyses were performed, respectively, to detect the independent predictors of survival.
  
  
  RESULTS
  Claudin-4 expression was present in only 7(15.9%) normal gastric samples, but expression of claudin-4 in the intestinal metaplasia lesions and dysplasia lesions was 90.5% and 95.2%, respectively. The expression of claudin-4 was significantly associated with histological differentiation (P < 0.001) and tumor growth patterns (P < 0.001) but not associated with patient survival. However, intermediate type staining of claudin-4 exhibited a trend of correlation with patients' survival (P = 0.023). The five-year survival rate with low expression of claudin-4 in intermediate type (76.4%) was similar to expanding type (64.5%), while the high expression group (46.6%) was closer to infiltrative type (50.7%).
  
  
  CONCLUSIONS
  The findings in this study demonstrate claudin-4 aberrant expression in gastric cancer and precursor lesions. The expression of claudin-4 could serve as a basis for identifying gastric cancer of the intermediate type.
authors.affiliation: Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, China.
authors.forename: Jin-Liang
authors.initials: JL
authors.lastname: Zhu
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.forename: Zhen-Ning
authors.initials: ZN
authors.lastname: Wang
authors.forename: Yong-Xi
authors.initials: YX
authors.lastname: Song
authors.forename: Ai-Lin
authors.initials: AL
authors.lastname: Li
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Xu
authors.forename: Mei-Xian
authors.initials: MX
authors.lastname: Wang
authors.forename: Hui-Mian
authors.initials: HM
authors.lastname: Xu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D062506:Claudin-4 / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008679:Metaplasia / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D062506:Claudin-4